Stem cells, especially ESC due to pleuripotency, are being investigated to repair or rejuvenate tissue. However ESC, due to their pleuripotential (also spelled pluripotent) behavior, when injected in vivo form teratomas, a dysregulated, cancerous tumor growth. Teratomas are composed of cells from all three embryonic germ layers: mesoderm, endoderm, and ectoderm.
To circumvent generation of teratomas, ESC presently used in transplantation must be differentiated ex vivo into lineage committed adult stem cell phenotypes and or fully differentiated cells. This process is time consuming, requires maintenance of Good Manufacturing Procedures (GMP) over an extended period of time, and a method to purify the final product to ensure there is no contamination from residual pleuripotent ESC, and a method to ensure desired cell identity and lot to lot equivalency. ESC-derived cells must be grown ex vivo and maintained in feeder free and defined-media conditions to meet GMP guidelines.
Recent advances in cell culture technology have met GMP requirements for maintenance and expansion of undifferentiated ESC. However, in order to avoid teratoma formation, ESC must undergo costly and labor intensive differentiation into a mature somatic cell prior to in vivo application. In addition, these somatic cells must undergo purification or selection to avoid contamination with residual teratoma forming ESC or other undifferentiated or differentiated contaminating cells.
Further advances in ESC technologies have been restrained due to governmental restrictions and ethical issues surrounding the use of human ESC. Of concern to many is the use of human ESC in medical procedures.
Notwithstanding the ethical issues surrounding ESC, patients who have received transplanted ESC produced by current methods may require lifetime immune suppression to prevent ESC derived somatic cell rejection. Immune suppression may be accomplished by the use of immunosuppressants. Immunosuppressants are a class of drugs capable of inhibiting the body's immune system. Many of the agents included in this category are also cytotoxic (cell poisons) and are used in the treatment of cancer. Cytotoxic agents used as immunosuppressants include antimetabolites (azathioprine), alkylating agents (cyclophosphamide), and folic-acid antagonists (methotrexate or 6-MP). Other immunosuppressants include mycophenolate (CellCept) and cyclosporin. These drugs may be used in ESC transplant patients to decrease the body's own natural defense to foreign bodies (such as the transplanted ESC) and thereby, attempt to prevent the ESC rejection by the body.
Suppression of the immune system may create a number of undesirable side effects in a patient such as stomach upset, nausea, vomiting, abdominal pain, mouth ulcers, darkened urine, pale stools, jaundice (yellowing of the skin or white portion of the eyes), unusual bleeding or bruising. A serious (and life threatening) side effect is reduced activity of bone marrow, which is monitored with regular blood tests. Occasionally, patients taking immunosuppressants will develop pancreatitis (inflammation of the pancreas) some months after starting these drugs.
Additionally, patients undergoing immunosuppression therapy are at a greater risk for various infections including bacterial infections, herpes infections (such as cold sores and shingles), cytomegalovirus, fungal infections, and Pneumocystis carinii (a lung infection). Because patients are at an increased risk for infection, they may be required to have routine assessments to check for any signs or symptoms of infection. To prevent illness, patients may be required to take anti-viral medications such as acyclovir, cytovene, and valacyclovir; anti-fungal medications such as fluconazole and voriconzaole; and antibiotics such as Bactrim.
Patients receiving immunosuppressant therapy will likely experience substantial changes in daily routine. Patients must be vigilant in avoiding persons and activities posing a risk of infection.
Patients may need to restrict the number of individuals with whom they come in contact with on any given day and avoid crowded, enclosed areas. Patients must avoid contact with friends and family who have been sick including school-aged children. If a member of the patient's immediate family is ill, the patient may be required to stay in another room or stay in a hotel until the family member is no longer sick. Patients must also avoid contact with babies and children who have been recently vaccinated with the live-virus oral polio vaccine for at least eight weeks. Recipients of the vaccine can shed the virus in body excretions such as saliva and stool and infect an immunosuppressed individual. Patients may be required to avoid crowed places such as restaurants, churches or temples, retail stores, and public transportation.
Patients may also be restricted from performing or engaging in certain activities which have a high risk for infection. These activities may include changing a baby's diaper, interacting with pets, and gardening.